The Invitae 3-Methylcrotonyl-CoA Carboxyalse Deficiency Panel analyzes the two genes that are associated with 3-Methylcrotonyl-CoA Carboxyalse (3MCC) deficiency. This test is useful for the diagnosis of patients who are suspected to have 3MCC deficiency according to clinical symptoms, biochemical findings, or abnormal newborn-screening results.
The Invitae Organic Acidemias Panel and the Invitae Elevated C5-OH Panel have been designed to provide a broad genetic analysis of these classes of disorders. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. They can be ordered at no additional cost.
Patients with 3MCC deficiency show a wide range of phenotypic severity, from asymptomatic to more severe. Traditionally, diagnosis relied on ascertainment of symptomatic patients. A wide range of symptoms have been reported, including developmental delay, intellectual disability, seizures, hypotonia, hypoglycemia, metabolic acidosis, ketosis, Reye syndrome, hyperammonemia, secondary carnitine depletion, and even coma or death; however, with the advent of expanded newborn screening, it is now recognized that the vast majority (>90%) of diagnosed individuals are asymptomatic, despite the presence of the characteristic biochemical abnormalities. No phenotype-genotype correlations exist, and recent studies have suggested that symptoms in at least some clinically affected individuals may have an alternative underlying cause.
Patients with 3MCC deficiency typically have biochemical laboratory findings, including elevations of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine on urine organic acid analysis; and elevation of 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening or plasma acylcarnitine analysis. Asymptomatic mothers may also be diagnosed due to elevated C5-OH in their healthy babies’ newborn-screening result.
Approximately 99% of patients with isolated 3MCC deficiency will have two pathogenic variants in either the MCCC1 or MCCC2 gene.
3MCC deficiency is inherited in an autosomal recessive pattern.
The general prevalence for 3MCC deficiency is estimated at 1 in 41,700–84,700 individuals.
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Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|